LP-04 Ninjurin-1 mediates epithelial–immune crosstalk in PM2.5-induced ocular surface toxicity

Exposure to fine particulate matter (PM2.5) is a major environmental risk factor that induces ocular surface toxicity and mucosal inflammation. However, the molecular pathways linking epithelial stress to immune dysregulation remain poorly defined. In this study, we identify Ninjurin-1 (Ninj1), a membrane-associated protein, as a key mediator of PM2.5-induced ocular toxicity. In a dry eye disease (DED) mouse model and PM2.5-exposed human corneal epithelial (HCE-T) cells, Ninj1 expression and oligomerization were significantly increased. In HCE-T cells, this was accompanied by upregulation of PANoptosis markers, including Caspase-1, MLKL, and Caspase-3. Genetic deletion of Ninj1 or intravitreal delivery of miR-125a-5p, a post-transcriptional suppressor of Ninj1, attenuated corneal damage and reduced the expression of inflammatory cytokines (TNF-α, IL-6, IL-1β) in vivo . Moreover, conditioned media from PM2.5-treated HCE-T cells promoted M1 polarization and adhesion of macrophages, effects that were diminished upon Ninj1 knockdown. These findings suggest that Ninj1 serves as a molecular link between epithelial injury and immune activation in response to airborne toxicants. Our results position Ninj1 as a novel therapeutic target for environmentally induced ocular surface disorders and mucosal toxicities.